1. University of Minnesota
Needed Research to Improve Care for People with Trigeminal Neuropathic Pains
Donald Nixdorf, DDS MS
Assistant Professor
University of Minnesota

2. What do YOU think? Knowledge of the Mechanisms Education
More Awareness in Primary Care (DDS & MD)
Better medications & treatments
More effective
Less side-effects
Improved Diagnostic Criteria
Based on WHAT?
Knowledge of the Mechanisms

4. H.M.S. Salisbury James Lind (1716-1794)
“The number of seaman in time of war who died of shipwreck, capture, famine, fire or sword, are but of inconsiderable in respect of such as are destroyed by the ship diseases, and by the usual maladies of intemperate climates.” – Dr. Lind, 1753

5. Symptoms of Scurvy lethargy irritability weight loss
aching of the joints
bleeding under the skin and nails
swollen and bleeding gums
spontaneous bruising
wounds slow to heal

6. Scurvy: Timeline
James Lancaster (sea captain) records lemon juice as protective against scurvy
British Admiral George Anson completes trip around the world in the Centurion . Over half of the 2,000 sailors die from scurvy
Lind’s experiment on the HMS Salisbury
Lind publishes “A Treatise of the Scurvy”
Captain James Cook completes historic voyages Sailors remained free from scurvy
British Navy supplies daily ration of lime or lemon juice
Waugh and King (U of Pittsburgh) and Szent Gyorgyi (Hungary) isolate and synthesize vitamin C

7. Discoverer of preventive measure
Disease
Discoverer of preventive measure
Year of discovery of preventive measure
Year of discovery of causal agent
Agent
Scurvy
J. Lind
1753
1932
Ascorbic acid
Scrotal cancer
P. Pott
1775
1933
Benzo(a)pyrene
Smallpox
E. Jenner
1798
1958
Orthopoxvirus
Puerperal fever
I. Semmelweis
1847
1879
Streptococcus
Cholera
J. Snow
1849
1893
Vibrio cholerae
Bladder cancer
L. Rehn
1895
1938
2-Naththylamine
Yellow fever
W. Reed et al
1901
1928
Flavivirus
Oral cancer
R. Abbe
1915
1974
N-nitrosonomicotine
Wynder EL. Am J Epidemiol 1994;

8. What we are looking for…
Epidemiologist
Scientist
Care Provider

9. What am I going to do…
Functional Magnetic Resonance Imaging
fMRI

10. High Resolution (post-MION) acquisition
Acquisition parameters:
TR/TE = 50/3.5 ms, readout bandwidth 20 kHz,
FOV 20 x 11.2 x 2.5 mm, matrix 384 x 216 x 16, 16 averages,
Acquisition time 2:53 min/scan, total time 46:08 min.
The image was reconstructed 2x zero-filling, producing a reconstructed resolution of 26 x 26 x 78 mm.
Bolan, Yacoub, Garwood, Ugurbil, Harel NeuroImage 2006 10

11. 3D Vessel Reconstruction Vessel Classification
blue = vein
red = artery
Bolan, Yacoub, Garwood, Ugurbil, Harel NeuroImage 2006 11

12. Maximum Intensity Projections (MIP)
MIP of the 3D subtraction (Pre/Post MION)
Bolan, Yacoub, Garwood, Ugurbil, Harel NeuroImage 2006 12

13. First human images at 9.4 Tesla
Vaughan et al., MRM 2006 13

14. Definitions Neuropathic Pain needs to fulfill the following criteria:
Pain presents in a neuranatomically defined area
History of a relevant disease or lesion in the nervous system (dental procedures)
Partial or complete sensory loss in all or part of the painful area
Confirmation of the lesion or disease by a specific test (i.e. surgical evidence, imaging, neurophys., biopsy)

15. Does persistent pain arise from surgery?
What are the factors that would put some patients at higher risk for developing persistent pain than others ?
What are the human neuroanatomical & functional mechanisms involved in this type of pain?
…multiple other research questions & steps…
What are viable interventions and when should they best be applied ? (pre-op, intra-op & post-op)
The basic questions I have that are not well answered in the literature, and they are:
2. It will likely require the development of a standardize questionnaire (history & comorbid psychosocial factors) and the application of a physiological test to reasonability identify, pre-operatively, patients who may be at increased risk from surgery in the trigemenally innervated structures of the orofacial region
…some of those multiple project include establishing a mechanism-based diagnostic classification system for trigeminal-mediated pain, as well as revising it to get it right
Planned studies to address these questions include
1. Collaborations with the Dental PBRN implementing study #1 and epidemiological work through the TNA
2. Pam Hughes & colleagues
3. K12 award – project support and didactic training related to research development of all levels
… Mark Drangsholt at the U of Washington
= and lastly, the area that I care about most – patient care issues. How do I make things better!
This is where you come in, as a referring source of research subjects needed for each step along this research career path. This is intended to be a “win-win” relationship with you sending patients that can benefit from my care, some of these participating as research subjects, and the knowledge gained return to you so that you may treat your future patients better

16. Procedures performed within U.S. (in 100,000/yr)
All General Surgeries
45,023
309
Nose/Mouth/Pharynx
All Dental Surgeries
55,874
40,036
Tooth Extractions
15,838
Root Canal Therapies
15,000
30,000
45,000
60,000
Data from the CDC (2004) & American Dental Association (1999)

17. Take Home 30% get persistent pain 10% are severely affected
Kehlet et al, 2006
in Lancet
Within the introduction of this articles, they authors stated that to date no large prospective cohort studies have been published reporting on the
Take Home
30% get persistent pain
10% are severely affected

18. SUMMARY Dental Procedures
Type of Procedure
# Studies in Literature
Post-op nerve damage
Persistent pain at 12 months
#’s seen in tertiary pain clinics
BSSO 4
~75%
(60-88%)
~4%
(0-6%)
some
3rd Molar Extraction 6
~5%
(0.5-8%)
<1%
(0-0.9%)
few
Root Canal Therapy
unknown
(3-13%)
several
Now, the data presented from theses studies are fraught with a plethora of design and methodological problems
retrospective in nature (bias introduced)
inclusion & exclusion criteria often not disclosed or improperly (pt w/ outcome enrolled)
varying definitions of nerve dysfunction (self-report vs. QST)
small sample sizes and lack of clinical relevance (representative population clinical practice & generalizability)

19. Procedures performed within U.S. (in 100,000/yr)
All General Surgeries
13,406 (30%)
93 (30%)
Nose/Mouth/Pharynx
All Dental Surgeries
1,676 (3%)
400 (1%)
Tooth Extractions
792 (5%)
Root Canal Therapies
15,000
30,000
45,000
60,000
Data from the CDC (2004) & American Dental Association (1999)

20. Pain & Oral Health Quality of Life: Measuring Success of Root Canal Therapy
Prospective cohort evaluating non-surgical root canal therapy 1 year after treatment
Aims:
Determine incidence of persistent pain at 1 year
Assess the burden on the individual
Evaluate the risk factors associated with developing this type of pain
AAE Research Priorities Research
A. Assessment of Clinical Outcomes
1. Factors affecting success of endodontic treatment
a. Nonsurgical and surgical endodontic treatment
2. Management of anxiety, infection, inflammation and pain

21. Why participate in practice-based research networks?
Generalizability
Sample size
Laboratory Clinical Practice-based Community-
research trials research based
in academic research
settings

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